Deletion of ABIN1-LIR motifs impairs hepatic lipid homeostasis and mitophagy via AMPK-TFEB axis in mice

Having identified LC3-interacting region (LIR) motifs 1/2 of A20 binding inhibitor of NF-κB-1 (ABIN-1) as mitophagy regulators in vitro, this study generated CRISPR-engineered ABIN1-ΔLIR1/2 mice lacking both LIR motifs to elucidate its in vivo significance. These mice exhibit enhanced hepatic lipid droplet accumulation, dysregulated mitochondrial metabolism, and impaired mitophagy, through modulation of the AMPK-TFEB axis. Liver biopsies from patients with metabolic dysfunction–associated steatotic liver disease corroborate these findings, suggesting therapeutic implications for liver diseases.